Abstract 522: Preoperative D-dimer and Tissue Factor activity predict postoperative venous thromboembolism in glioma patients
Authors: Amanda Alexander, Michael Drumm, Jonathan Lamano, Rodrigo Javier, Kathleen McCortney, Rachel Weller Roska, Kirsten Burdett, Denise M. Scholtens, Nathan Steere, Amanda Kubik, Yoav Noam, Craig Horbinski, Dusten J. Unruh
Journal: Cancer Research (2022)

Abstract Background: Venous thromboembolism (VTE) is a debilitating and life-threatening condition that is common in patients with cancer, especially glioma. There are no widely-accepted antithrombotic prophylaxis guidelines for glioma patients, partly because of the risk of iatrogenic intracerebral hemorrhage. Effective VTE risk assessment models exist for other cancers, but not glioma. Our prior publications suggested a protective role of IDH1 mutations (IDHmut) against VTE, and a direct correlation between circulating Tissue Factor (TF), a procoagulant secreted by cancers, and VTE in glioma patients. Others have found a correlation between inflammatory markers and cancer-associated VTE, but this has not yet been proven in gliomas. Our objective was to evaluate glioma patients for increased VTE risk by assessing clinical, histologic, molecular, and plasma-based markers. Methods: The Northwestern University Nervous System Tumor Bank provided preoperative arterial plasma, tumor tissue, and clinical-pathological data from 165 newly diagnosed glioma patients. Molecular profiling was done by GlioSeq NGS. Twelve candidate VTE biomarkers (D-dimer, E-Selectin, ICAM-1, VCAM-1, Granzyme B, IFNγ, TNFα, IL-2, IL-4, IL-6, IL-10, and IL-13) were analyzed using the automated microfluidic multiplex Ella࣪ platform. TF procoagulant activity was measured using a FXa chromogenic assay. Results: Of these patients (n=165), 33 (20%) experienced post-operative VTE. Clinical characteristics associated with increased VTE risk included advanced patient age, high body mass index, high tumor grade, prior history of VTE, coronary artery disease, hyperlipidemia, and hypertension. Of the targeted genetic screening panel (GlioSeq) on resected tumors, only IDHmut significantly correlated with VTE, being associated with reduced risk (OR=0.28; 95% CI=0.12-0.64, P=0.001). Among the plasma biomarkers, elevated circulating TF activity and D-dimer correlated with VTE risk. Circulating TF (&amp;gt;2.0pg/mL) was associated with VTE (Log-rank, P=0.002). D-dimer was elevated in patients that developed VTE (1,355±2,000 vs 605±1,061 ng/mL; P=0.004). High levels of D-dimer associated with worse median overall survival (2.5 vs. 46.9 months; Log-rank P&amp;lt;0.0001), and high D-dimer also developed VTE events quicker (95 vs 245 days; Log-rank P=0.001). Conclusions: This study identified multiple risk factors for glioma-associated VTE and may help identify which patients would benefit the most from prophylactic anticoagulation therapy following surgery. Citation Format: Amanda Alexander, Michael Drumm, Jonathan Lamano, Rodrigo Javier, Kathleen McCortney, Rachel Weller Roska, Kirsten Burdett, Denise M. Scholtens, Nathan Steere, Amanda Kubik, Yoav Noam, Craig Horbinski, Dusten J. Unruh. Preoperative D-dimer and Tissue Factor activity predict postoperative venous thromboembolism in glioma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 522.